In an unbiased genetic screen designed to isolate mutations that affect synaptic transmission, we have isolated homozygous lethal mutations inDrosophila importin 13(imp13). Imp13 is expressed in and around nuclei of both neurons and muscles. At the larval neuromuscular junction (NMJ),imp13affects muscle growth and formation of the subsynaptic reticulum without influencing any presynaptic structural features. In the absence ofimp13, the probability of release of neurotransmitter and quantal content is increased, yet the abundance of the postsynaptic receptors and the amplitude of miniature excitatory junctional potentials are not affected. Interestingly,imp13is required in the muscles to control presynaptic release. Thus,imp13is a novel factor that affects neurotransmitter release at the fly NMJ. Its role in the context of synaptic homeostasis is discussed.